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Are antibiotics useful in the management of nontoxic severe ulcerative colitis?

Severely ill patients with ulcerative colitis are usually treated with parenteral corticoids. Those with signs of systemic toxicity usually receive antibiotics as well. However, the role of antibiotics in patients without high fever, profound leukocytosis, peritoneal signs or megacolon is not clear. Since 1985, seven patients who were admitted to the hospital with severe ulcerative colitis but without signs of toxicity have received broad spectrum antibiotics. The patients ranged in age from 21 to 65 years: four were male; all were white. Stools for infectious agents were negative. Each patient received intravenous prednisolone at a dose of 60 mg/24 h. After 7 days, each patient continued to have eight to 10 bloody stools per day with low-grade fever and leukocytosis. Institution of broad-spectrum antibiotics was associated with a striking resolution of bloody diarrhea and normalization of temperature. No patient has required colectomy in follow-up of 2-9 years. Whether the antibiotics are treating an undetected pathogen or eliminating non-pathogenic bacteria contributing to the inflammatory process is not clear. I suggest that severely ill patients with ulcerative colitis deserve a trial of antibiotics before being considered failures of medical therapy.

Acute Disease↗

Absence of plasma protease-antiprotease imbalance in the formation of saccular cerebral aneurysms.

OBJECTIVE: We examined the hypothesis that a plasma protease-antiprotease imbalance contributes to the formation of saccular cerebral aneurysms and the suggestion that the assay of these enzymes might be a screening tool for people at higher risk for aneurysm formation. METHODS: From June 1997 through May 1998, the plasma leukocyte elastase, which is an important proteolytic enzyme, and alpha-antitrypsin and alpha2-macroglobulin, which are important antiproteolytic enzyme plasma proteins, were examined in 18 patients with ruptured aneurysms, 9 patients with unruptured aneurysms, and 22 controls. RESULTS: The elastase:alpha1-antitrypsin ratio and the elastase:alpha2-macroglobulin ratios were significantly higher in patients with ruptured aneurysms within 24 hours after subarachnoid hemorrhage (SAH) than in the controls. The protease-antiprotease imbalance depended on the elevation of the elastase level, which might be correlated with leukocytosis after SAH. The elastase level decreased to the control level 3 months after the onset of SAH. No significant difference in the elastase:alpha1-antitrypsin and elastase:alpha2-macroglobulin ratios was observed between the patients with unruptured aneurysms and the controls. CONCLUSION: These results do not support the hypothesis that a plasma protease-antiprotease imbalance is a potential marker to predict the formation of saccular cerebral aneurysms. The increase in plasma elastase levels in patients with ruptured aneurysms might be attributable to leukocytosis after SAH.

Adult↗

The value of routine cultures of the cerebrospinal fluid in patients with external ventricular drains.

OBJECTIVE: The purpose of this study was to determine whether routine cerebrospinal fluid (CSF) bacteriological cultures in patients with external ventricular drains (EVDs) can identify infections early and prevent complications related to bacterial ventriculitis. METHODS: We retrospectively reviewed the microbiological reports and clinical data for all patients in whom an EVD was placed at a tertiary care pediatric neurosurgical center between 1984 and 1997. EVDs were inserted in the operating room or intensive care unit, and, in most patients whose EVD remained in place for more than 2 days, daily cultures of CSF were performed. RESULTS: One hundred fifty-seven patients in whom 160 EVDs had been placed were included in the study. Forty-eight positive cultures were identified, of which the majority were determined to be contaminants. Seven infections were identified on the basis of microbiological criteria (i.e., a gram-positive stain and positive culture) and a subsequent positive culture. In all patients in whom infections developed, routine daily cultures of CSF were performed, and, in each instance, these cultures failed to identify the infections before clinical changes occurred. All seven patients with infection had fever (>38.5 degrees C) and peripheral leukocytosis (>11 x 10(3)/mm3) on the day the infection was identified, and one had a change in CSF appearance. CONCLUSION: The results of this study suggest that routine culture of CSF in children with EVDs is not necessary, and that if CSF cultures are performed for new fever (>38.5 degrees C) or peripheral leukocytosis, neurological deterioration, or a change in CSF appearance, infections will be identified in a timely fashion. In situations in which these clinical indicators might be masked, routine cultures may be valuable.

Adolescent↗

Murine typhus in South Texas children.

BACKGROUND: Murine typhus is a zoonotic infection caused by Rickettsia typhi. This illness used to be endemic in the southeastern and gulf coast of the United States and is now only rarely reported in South Texas and Southern California. Murine typhus causes a febrile illness with headache and rash that has been well-described in adults. OBJECTIVE: To define the epidemiologic and clinical characteristics, laboratory findings, hospital course and response to therapy of children discharged from our hospital with a diagnosis of murine typhus. METHODS: Retrospective chart review of all children discharged from Driscoll Children's Hospital, Corpus Christi, TX, from January 1, 1990, to June 30, 1998, with a diagnosis of murine typhus. Patients. Thirty children (17 females) ages 2 to 17 years (mean, 10 +/- 4 years). RESULTS: Eighty percent of the children were admitted between May and November, and 67% had a history of contact with or exposure to a potential animal reservoir. Children were admitted after a mean of 7 +/- 4 days. The most common clinical features were fever 100%, rash 80% and headache 77%. Laboratory abnormalities included elevated erythrocyte sedimentation rate (75%), elevated serum transaminases (67%), hyponatremia (66%) and increased immature leukocytes without leukocytosis (63%). Only one child had leukocytosis and 40% had leukopenia. Defervescence occurred a mean of 35 +/- 19 h after initiation of appropriate antibiotics. Hospitalization lasted for a mean of 7 +/- 3 days. There were no readmissions and no patients died as a result of the infection. CONCLUSIONS: Despite being rarely reported in this country now, murine typhus continues to be an important cause of fever and hospitalization for children in South Texas. Children with murine typhus develop an illness similar to that reported in adults with fever, rash and headache. Children respond quickly to therapy with doxycycline or tetracycline and recover completely from their illness.

Adolescent↗

Cryptogenic mycotic aneurysm of the right coronary artery.

A 61-year-old man with chest pain and fever was referred to our hospital. The physical examination and electrocardiogram were unrevealing. Laboratory tests showed leukocytosis, and echocardiography showed mild pericardial effusion. The patient died soon after hospital admission. Necropsy revealed ruptured mycotic aneurysm of the right coronary artery in the absence of infective endocarditis. Thus, mycotic aneurysm of the coronary artery may occur without infective endocarditis and may be clinically manifested as pericarditis and leukocytosis.

Aneurysm, Infected↗

Philadelphia chromosome-positive chronic myeloid leukemia and thoracic ganglioneuroma. Previously undescribed association.

A previously healthy 11 year-old-white boy presented with persistent mild leukocytosis and a posterior mediastinal mass. Surgical excision of the mass showed it to be a ganglioneuroma. Postoperatively, the patient had marked leukocytosis (white blood cell count 57,000/mm3) and a low leukocyte alkaline phosphatase score. Bone marrow aspirate for cytogenetics performed in the evaluation of the posterior mediastinal mass showed the presence of the Philadelphia chromosome (Ph) in 19 of 20 metaphase spreads. The diagnosis of Ph+ chronic myeloid leukemia (CML) was confirmed on repeat cytogenetics. Subsequent detailed skin examination showed six small cafe-au-lait spots but no other evidence of neurofibromatosis. This is the first report to describe an association between ganglioneuroma and Ph+ CML.

Child↗

Human models of endotoxemia and recombinant human activated protein C.

OBJECTIVES: To review human models of endotoxemia with an emphasis on the inflammatory and coagulopathic effects of lipopolysaccharide to describe the possible mechanisms of clinical benefit of recombinant human activated protein C (drotrecogin alfa [activated]) in severe sepsis. DATA SOURCE: A selected review of published literature in English on human endotoxemia models with special attention to studies using drotrecogin alfa (activated) in concert with endotoxemia. DATA EXTRACTION AND SYNTHESIS: After intravenous administration of purified lipopolysaccharide, subjects report constitutional influenza-like symptoms associated with an increase in temperature. Within 1 hr of lipopolysaccharide infusion, total leukocyte counts decline. Sustained leukocytosis, due to an increase in neutrophils counts, follows. An increase in markers of neutrophil activation (e.g., serum elastase) accompanies this leukocytosis. Production of tumor necrosis factor-alpha, interleukin-6, and interleukin-8 is also increased. In association with an inflammatory response, lipopolysaccharide administration also activates the coagulation system. Lipopolysaccharide infusion generates thrombin and initially activates fibrinolysis but subsequently generates inhibitors of the fibrinolytic system. Serum levels of endogenous inhibitors of coagulation (e.g., antithrombin, protein C, tissue factor pathway inhibitor) are not affected. Data are available for 40 subjects who have participated in placebo-controlled studies of drotrecogin alfa (activated) infusion before an intravenous dose of lipopolysaccharide. In these subjects, drotrecogin alfa (activated) has minimal effects on measured variables, including physiologic variables, markers of inflammation, and measures of sepsis-induced coagulopathy. CONCLUSION: Human endotoxemia is, at best, an incomplete model of human sepsis. In two studies using recombinant human activated protein C in the setting of human endotoxemia, there were minimal effects on hemodynamics, inflammation, thrombin generation, fibrinolysis, and markers of cellular activation. Other putative mechanisms of recombinant human activated protein C, such as inhibition of apoptosis and leukocyte recruitment, remain to be studied.

Anti-Infective Agents↗

Detection of free hepatitis C virus core antigen by enzyme-linked immunosorbent assay is not suitable for screening of granulocyte colony-stimulating factor-mobilized hematopoietic progenitor donors.

BACKGROUND: Recent studies have shown that hepatitis C virus (HCV) can be detected in peripheral blood mononuclear cells of patients who are negative for the presence of anti-HCV and serum HCV RNA. The aim of the study was to evaluate the prevalence of HCV viremia in granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cell (PBPC) donors by the use of a free HCV core antigen enzyme-linked immunosorbent assay (ELISA). STUDY DESIGN AND METHODS: A total of 28 samples from consecutive PBPC donors that were mobilized with G-CSF, and 13 samples from patients presenting with leukocytosis of greater than 20 x 10(9) per L from other causes, were tested by a free HCV core antigen ELISA. Positive samples were confirmed by use of neutralization assays. The specificity of the assay was studied in 48,911 healthy blood donors negative for the presence of anti-HCV. RESULTS: The free HCV core antigen assay showed a 46.4 percent positivity in PBPC donors mobilized with G-CSF and 61.5 percent in patients exhibiting leukocytosis in the absence of G-CSF treatment. All the samples were found to be false-positive samples, and those related with growth factor treatment did not react when G-CSF was discontinued. Overall specificity by the test in freshly collected blood donor specimens was 99.62 percent. CONCLUSION: Data indicate that the free HCV core antigen ELISA is not a valid test in diagnosing HCV infection in G-CSF-treated PBPC donors. Moreover, false-positive results of this test on blood donors might be indicative of elevated white blood cell numbers. The low specificity of this assay in the PBPC mobilization setting suggests that molecular assays should be the test of choice in the screening of G-CSF-treated donors.

Adolescent↗

Evaluation of tonsillectomy as a treatment for pustulosis palmaris et plantaris.

Two hundred and eighty five cases of pustulosis palmaris et plantaris (PPP), of which 73 cases (25.6%) underwent tonsillectomy, were studied to evaluate the effectiveness of tonsillectomy as a treatment for PPP. The group of tonsillectomized patients showed significantly better results than a group which received other methods of treatment. A tendency to leukocytosis was observed in PPP which normalized, in many cases, after tonsillectomy. The shorter the period between the onset of PPP and tonsillectomy the better the results, and the quicker the response. A transient worsening of PPP after tonsillectomy did not after the prognosis. In order to determine if tonsillectomy was indicated, an ultrashort wave direct provocation test was conducted in which ultrashort wave was applied to the tonsil. Leukocytosis and worsening of PPP after the test was considered as an indication for tonsillectomy. In some cases, there were considerable changes in plasma cortisol levels and NBT test values after the provocation test. Improvement of PPP after the Impretol test (one of the annulation tests) in which Impretol was injected into the tonsil, appears to support the focal infection origin of PPP in these cases. There is a possibility that the Impretol test could be used as a treatment for PPP.

Adult↗

Clinical, pharmacological and immunological aspects of delayed pressure urticaria.

We studied the clinical features of thirty-two patients with delayed pressure urticaria, and special laboratory tests were performed in seven patients. Striking clinical features included a long duration of the disease (mean 6 years) and an elevated erythrocyte sedimentation rate in 71%, dermographism in 63% and a leukocytosis in 33% of the patients. There was prolongation of weals in response to histamine, compound 48/80, concanavalin A and NaCl. In some patients, histamine and chemotactic factor levels were increased in suction blisters over skin test and delayed pressure sites. In extracts from pressure weals, chemotactic activity was found for leukotriene B4, its 20-omega-oxidation products and mono-HETEs. Studies of peripheral blood leukocytes revealed significantly increased intracellular histamine levels and increased release of histamine, and a trend to increased release of chemotactic activity from stimulated cells. The response of leukocytes to mitogens was normal. We conclude that histamine plays a major role in the pathogenesis of PU. Arachidonate-derived chemotactic factors might account for the variably observed leukocytosis and the cellular infiltrate in lesions of pressure urticaria. Additional mediators must be involved in PU in order to explain the unique prolonged wealing response.

Adult↗

Production and characterization of recombinant active mouse gelatinase B from eukaryotic cells and in vivo effects after intravenous administration.

Gelatinase B is a matrix metalloproteinase involved in tissue remodelling. When mouse cells are triggered in vitro with interleukin-1, bacterial endotoxin, virus-mimicking double-stranded RNA or cytokine inducers, they produce gelatinase B. To test the effects of gelatinase B in vivo, the enzyme was expressed in Chinese hamster ovary (CHO) cells. Hybrid genomic DNA-cDNA constructs under the control of two constitutive viral promoters were generated by PCR-mediated exon amplification. In vitro transcription and translation of the mRNA in reticulocyte lysate yielded the correct 79-kDa protein, and expression in CHO cells resulted in an intact glycosylated 110-kDa gelatinase B which was enzymically active. However, the production yields of recombinant enzyme from 50 tested clones were low and cell-culture supernatants contained significant amounts of copurifiable endogenous CHO gelatinase B. Therefore, the enzyme was expressed in the yeast Pichia pastoris. Recombinant proenzyme was secreted and recovered from the yeast culture medium at 10 mg/l. Amino-terminal sequence analysis indicated that affinity purification of the recombinant protein on gelatin-Sepharose yielded the expected N-glycosylated proenzyme form (110 kDa) in addition to an amino-terminally truncated unglycosylated variant (69 kDa). Both forms had gelatinolytic activity on zymography. The recombinant mouse gelatinase B was used to determine its pharmacokinetics and its haematological effects in vivo. After intravenous injection in rabbits, gelatinase B disappeared from the circulation within 6 h. In addition to a transient leukopenia, we observed a rapid increase in leukocytosis, which indicates that gelatinase B might be a factor involved in the desorption of adherent leukocytes from the vascular bed and in the release of leukocytes from the bone marrow. Gelatinase B secretion and activation might well be one of the crucial molecular mechanisms explaining leukocytosis which is associated with infections and almost all types of inflammation.

Animals↗

Silent infection in male accessory genital organs and male infertility.

A silent infection of the male accessory genital organs was found in the semen of 78 patients (22,3%) of 350 infertile men. All the sperm characteristics (except agglutination) were significantly deteriorated in the infection group as compared to the sperm of 36 normal men. The volume was significantly larger than normal. In this group there was significant leukocytosis and, as a sign of prostatic hypofunction, reduced seminal acid phosphatase and citric acid activity. Chemotherapy for a period of two to four weeks improved leukocytosis and sperm transiently. Only acid phosphatase was normal three months after the treatment. Suggested reasons for the infertility of the silent infection group are: 1. hypofunction of the male genital organs, caused by a primary, strong infection suffered earlier. 2. The chronic, nonclinical infection of the male accessory genital organs, mainly as a complication of the primary infection. Chemotherapy for a period of four weeks seems to be too short to correct the silent infection as well as the infertility.

Acid Phosphatase↗

Infertility and chronic prostatitis.

Long term treatment of chronic prostatitis with antimicrobials and their influence on semen quality and infertility were studied in 30 men with mean age of 36.7 +/- 6 years. The infection was symptomatic only in 50% of the patients with abnormal prostatic physical findings in 66.7%. Cardinal findings in the spermatogram were leukocytosis in 100% and oligoasthenozoospermia in 66.5% of the patients. E. coli and Staphylococci presented the most commonly isolated bacteria in prostatic secretion cultures. Various treatment schedules, including mostly co-trimoxazole, doxycycline and erythromycin, were given alternatively for 6-8 months. Symptoms were cured or improved in 79.7%, with elimination or improvement of abnormal physical findings in 85%, while the isolated pathogens were eradicated in all. Spermatograms were normalized or improved in 70% of the patients, while among them 9 impregnated their wives and in 2 of them twice. It is concluded that male infertility in the presence of semen leukocytosis and oligoasthenozoospermia should be investigated for underlying chronic prostatitis, while whenever proved, long term treatment with the proper antimicrobials not only cures or improves chronic prostatitis, but subsequently cures or improves male infertility.

Adult↗

Clinical aspects of pneumonia in the elderly veteran.

While atypical presentation of pneumonia in elderly patients is thought to be common, its incidence and factors predisposing to it are unknown. This study documents presenting symptoms of pneumonia in 48 patients, aged 65 or older, admitted to the medical service at a Veterans Administration Medical Center. Seventeen subjects (35%) had a classic constellation of symptoms which included both fever and cough. A chief complaint suggestive of pneumonia, defined as cough, fever, or shortness of breath, occurred in 27 subjects (56%). Five subjects (10%) had no symptoms suggestive of pneumonia even with a detailed history. Absence of a classic constellation of pneumonia symptoms correlated with advanced age (P = .0045), cognitive impairment at admission (P = .022), and baseline functional impairment (P = .028). Neither nutritional status as measured by serum albumin nor medical status as measured by number of medical problems and number of medications predicted an atypical presentation of pneumonia. Nineteen subjects (39%) did not have a documented fever, and 15 subjects (31%) did not have a leukocytosis. Absence of fever or leukocytosis did not correlate with age, number of medical problems, number of medications, cognitive status, functional status, or serum albumin. We conclude that a classic constellation of symptoms, signs and laboratory findings is frequently absent but some suggestive symptom is usually present in this population of elderly veterans with community-acquired pneumonia. Patients with advanced age, cognitive impairment at admission, and baseline functional impairment are most likely to have an atypical presentation of pneumonia.

Aged↗

Abdominal pain in geriatric emergency patients: variables associated with adverse outcomes.

OBJECTIVE: To determine the diagnoses and outcomes of geriatric patients with abdominal pain, and to identify variables associated with adverse outcomes. METHODS: Geriatric emergency patients (aged 65 years and older) with a complaint of abdominal pain were participants in this longitudinal case series. Eligible patients were followed by telephone contact and chart review, to determine outcomes and final diagnoses. RESULTS: Of 380 eligible patients, follow-up information was available for 375 (97%), for the two months following the ED visit. Final diagnoses included infection (19.2%), mechanical-obstructive disorders (15.7%), ulcers/hypersecretory states (7.7%), urinary tract disease (7.7%), malignancy (7.2%), and others. Although 5.3% of the patients died (related to presenting condition), most (61.3%) patients ultimately recovered. Surgical intervention was required for 22.1% of the patients. Variables associated with adverse outcomes (death, and need for surgical intervention) included hypotension, abnormalities on abdominal radiography, leukocytosis, abnormal bowel sounds, and advanced age. Most physical examination findings were not helpful in identifying patients with adverse outcomes. This study demonstrated a higher incidence of malignancy (7.2%) and a lower incidence of disease necessitating surgical intervention (22.1%) than previously reported. CONCLUSIONS: The majority of geriatric emergency patients with abdominal pain have significant disease necessitating hospital admission. Morbidity and mortality among these patients are high, and specific variables are strongly associated with death and the need for surgical intervention. Absence of these variables does not preclude significant disease. Physical examination findings cannot reliably predict or exclude significant disease. These patients should be strongly considered for hospital admission, particularly when fever, hypotension, leukocytosis, or abnormal bowel sounds are present.

Abdomen, Acute↗

Dynamics of cytokine production during coccidial infections in chickens: colony-stimulating factors and interferon.

We assayed two classes of immunoregulatory cytokines, colony-stimulating factors (CSF) and interferon (IFN), during and immediately after a primary coccidial infection in chickens. Coccidial infection induces significant alterations in serum colony-stimulating activity (CSA) and these alterations immediately precede the characteristic biphasic leukocytosis. CSA rose sharply during the first 24 h post-inoculation (PI), but returned to control levels by 48 h PI. At this time, we detected an increase in peripheral blood leukocytes which peaked at 96 h PI. A second phase of CSA increase began 96 h PI and peaked at 120-144 h PI which again preceded the second phase of leukocytosis. We also examined the production of IFN during the first 20 days PI. Splenic T cells from Eimeria maxima-infected chickens produced significantly less IFN on day 5 PI compared to T cells from the coccidia-free controls. By days 10 and 15 PI, there was no significant difference in IFN production between the T cells of infected and non-infected chickens. However, by day 20 PI, IFN production by the T cells of the infected birds produced significantly more IFN than the control T cells. The results of our studies indicated the differential production of two different cytokines by chickens during and following a primary coccidial infection. Based on these experiments, CSF may be some of the first cytokines produced during an E. maxima-infection, while IFN may be one of the later cytokines produced.

Animals↗

Clinical impact of internal tandem duplications and activating point mutations in FLT3 in acute myeloid leukemia in elderly patients.

BACKGROUND: The FLT3 gene is frequently mutated in acute myeloid leukemia (AML), either by an internal tandem duplication (ITD) of the juxtamembrane domain or by activating point mutations in the second tyrosine kinase domain (ATKD). Only a few investigations have focused on the prognostic significance of FLT3 alterations in AML among the elderly, yielding conflicting results. In the present study, the frequency and clinical relevance of FLT3 abnormalities were ascertained in a cohort of elderly AML patients. PATIENTS AND METHODS: A total of 109 AMLs, occurring in patients above the age of 60 yr (median 71.5), were investigated. DNA was extracted from fresh bone marrow cells or from cells in fixative and investigated for the presence of ITD of exons 14 and 15 and the ATKD D835 in exon 20. RESULTS: ITDs and ATKDs were identified in 20 (18%) and 11 (10%) of the cases, respectively. Three cases displayed both an ITD and an ATKD. FLT3 abnormalities were associated with leukocytosis (ITD P < 0.01; ATKD P = 0.069), and the monocytic FAB subtypes M4 and M5 [ITD (P < 0.05), ATKD (P = 0.05)], and ITD and ATKD were significantly (P < 0.05) more common in cases with a normal karyotype. There was no correlation between the presence of FLT3 abnormalities and complete remission rates or overall survival. CONCLUSION: A correlation was observed between FLT3 abnormalities and leukocytosis, a normal karyotype, and the M4/M5 subtypes of leukemia. However, no clear-cut prognostic impact of FLT3 abnormalities was identified in elderly AML patients.

Acute Disease↗

Long-term analysis of the palliative benefit of 2-chlorodeoxyadenosine for myelofibrosis with myeloid metaplasia.

OBJECTIVE: Therapeutic splenectomy in myelofibrosis with myeloid metaplasia (MMM) may result in extreme thrombocytosis and leukocytosis and accelerated hepatomegaly. We previously described initial palliative benefit from 2-chlorodeoxyadenosine (2-CdA) in such instances. The purpose of this study is to provide long-term follow-up on the durability of response in the initial cohort and in additional subsequent cases. METHODS: We retrospectively identified patients with histologically confirmed MMM who had palliative therapy with 2-CdA. Clinical characteristics and information on subsequent clinical course were abstracted at the time of diagnosis of MMM and at initiation of 2-CdA therapy until death. RESULTS: To date, we have used 2-CdA as palliative therapy in 14 patients with MMM. After a median of four cycles of therapy, responses for hepatomegaly occurred in 56% of patients, thrombocytosis 50%, leukocytosis 55%, and anemia 40%. Cytopenias were frequent but usually transient and without clinical consequence. Responses occurred usually by the second cycle; median duration of response was 6 months (range, 2-19) after completion of 2-CdA therapy. CONCLUSION: This study confirmed relevant and frequently durable palliation of symptoms in about half the patients. 2-CdA is a reasonable palliative option in postsplenectomy patients with MMM who have problematic myeloproliferation.

Adult↗